Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Towards a proteome-scale map of the human protein-protein interaction network.
Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.
Structural and functional analyses of human tryptophan 2,3-dioxygenase.
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Crystal structure of apo (heme-free) human TDO at 2.90 Angstrom; the enzyme assembles into a tetramer and mutational analysis identified eight active-site residues critical for L-tryptophan oxidation.
"Here, we report the crystal structure of human TDO (hTDO) without the heme cofactor to 2.90 Å resolution."
A proteome-scale map of the human interactome network.
Widespread macromolecular interaction perturbations in human genetic disorders.
Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase.
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Crystal structures of human TDO in ternary complex with L-Trp and O2 and in binary complex with the product N-formylkynurenine define catalysis; TDO catalyzes the first and rate-limiting step of the kynurenine pathway.
"TDO and IDO are heme proteins that catalyze the oxidative cleavage of L-Trp (Supplementary Fig. 1), the first and rate-limiting step of the kynurenine pathway for L-Trp catabolism"
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The majority of dietary tryptophan is catabolized in the liver through the kynurenine pathway to produce NAD+.
"The majority of dietary Trp (~95%) is metabolized in the liver through this pathway to produce NAD+"
Hypertryptophanemia due to tryptophan 2,3-dioxygenase deficiency.
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First human case of hypertryptophanemia due to TDO deficiency; recombinant human TDO expressed and shown to be catalytically active (kcat 0.54/s, Km 132 uM for L-Trp for wild-type).
"similar to 0.54 ± 0.02 s−1 for the wild-type, but the Km value was noticeably increased at 236 ± 39 μM, compared to 132 ± 25 μM for the wild-type"
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TDO is mainly hepatic, has high L-tryptophan substrate specificity, and its activity is increased by substrate, in contrast to the widely distributed, inflammation-induced IDO1.
"TDO, encoded by the TDO2 gene, is mainly expressed in the liver, has high substrate specificity for L-tryptophan, and its activity is increased by the substrate"
Architecture of the human interactome defines protein communities and disease networks.
Development of a mass spectrometry-based tryptophan 2, 3-dioxygenase assay using liver cytosol from multiple species.
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Active TDO2 enzyme is present in liver cytosol and can be assayed directly for L-tryptophan-to-kynurenine conversion, supporting a cytosolic localization.
"liver cytosol contained sufficient active TDO2 for evaluating the potency of TDO2 inhibitors across multiple species"
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Sequence of human tryptophan 2,3-dioxygenase (TDO2): presence of a glucocorticoid response-like element composed of a GTT repeat and an intronic CCCCT repeat.
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Reports the human TDO2 cDNA sequence and a glucocorticoid-response-like element in the gene, consistent with glucocorticoid regulation of the enzyme.
"Sequence of human tryptophan 2,3-dioxygenase (TDO2): presence of a glucocorticoid response-like element"
TDO tetramer dioxygenates L-Trp to NFK
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Cytosolic TDO tetramer converts L-tryptophan and oxygen to formylkynurenine; hepatic, induced by tryptophan, histidine and glucocorticoids; functions in tryptophan catabolism and NAD biosynthesis.
"Cytosolic tryptophan 2,3-dioxygenase (TDO) tetramer catalyzes the conversion of L-tryptophan and oxygen to formylkynurenine."